Keratoconus is a degenerative disease of the cornea that is a major cause of reduced vision-related quality of life in the United States, often leading to corneal transplantation. Ectasia after refractive surgery is a vision-threatening complication that can occur in apparently low-risk patients despite current screening technology. The biomechanical properties of the cornea play a central role in these diseases, but diagnostics are still rooted in shape measures because doctors lack direct measures of biomechanical change. While several methods have shown early promise for addressing this gap, most require contact with or perturbation of the cornea, cannot spatially resolve biomechanical properties, or involve expensive optical systems. To address the need for direct biomechanical measurement of the cornea and the limitations of other approaches, we introduce phase-decorrelation OCT (phd-OCT). Phd-OCT makes use optical coherence tomography (OCT) to quantify random nanoscale mobility that is related to the strength and cohesion of the cornea. Preliminary results strongly support the rationale, feasibility and potential advantages of the approach. Our objectives are: (1) to refine our method to optimize detection sensitivity and speed, and (2) to determine if the technique is clinically useful. We will achieve these objectives through the following aims: 1. To develop and validate mobility-sensitive phd-OCT for corneal imaging. Spectral-domain OCT will be used for anterior segment phase-decorrelation imaging and the analysis algorithm will be optimized. The system will be validated using phantoms and torsional rheometry. 2. To investigate the potential influence of physiological factors (intraocular pressure (IOP), hydration, and temperature). Factorial design experiments in porcine and human donor globes will establish the sensitivity of phd-OCT measurements to potential confounders. 3. To develop and validate data acquisition and processing methods to enable clinical testing. GPU processing and machine learning will be configured to minimize processing time. Scan patterns will be optimized to minimize scan time and return clinically useful data. 4. To assess feasibility and preliminary diagnostic performance of clinical mobility-sensitive OCT imaging of the cornea. A first-in-human study will characterize repeatability and test the hypotheses that phd-OCT mobility measurements are increased in the region of a LASIK flap and decreased in CXL. Expected Outcomes: The proposed studies will establish a new, non-contact method for imaging corneal biomechanical properties with the potential to address many shortcomings of current and emerging methods. Success could lead to earlier detection of of ectasia risk and allow more appropriate timing and customization of corneal treatments. Future integration of data into computational models has the potential to greatly impact the field by driving a shift from empirical planning and risk analysis to patient-specific strategies.